Neurogenic bladder dysfunction (NBD) is a significant public health problem, and a challenging area of urologic diagnosis and management. Two issues central to the problem are: (1) the lack of detailed information on the nature of intrinsic defects of muscular innervation in the dysfunctional bladder and urethra; (2) the very limited knowledge of mechanisms of neurotransmission in the vesicourethral musculature. This study addresses both of the above issues by a multimodal morphologic approach that has not been applied previously for this purpose. Short- and long-term changes in the neurohistochemistry and ultrastructure of muscular innervation in the detrusor, internal sphincter and rhabdosphincter (external urethral sphincter), in 6 experimental models of parasympathetic lower motoneuron-type NBD, will be analyzed both qualitatively and quantitatively, as a prelude to future morphologic study of human NBD. Correlation of the findings with a parallel analysis of innervation parameters in normal musculature using the same multimodal approach will provide new information relative to the first issue, namely, the nature of intrinsic defects of muscular innervation in the dysfunctional bladder and urethra. A subsequent correlative analysis of all morphologic data with available physiopharmacologic observations on normal and abnormal micturition will provide further new information relative to the second issue, namely, the structural basis of neurotransmission in the vesicourethral musculature. The results of the proposed study will thus fill important gaps in our knowledge of the neuromuscular basis of normal and abnormal micturition, and provide the hitherto lacking data base for the long-term objective, namely, the clinical morphologic study of muscular innervation in NBD in man, including that due to spinal cord injury. Such a study would eventually lead to the introduction of: (1) a clinical biopsy tissue test as an aid to diagnosis, treatment planning and follow-up; and (2) drug therapy options that are more selective, effective and predictable than has so far been available.